CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Hypoxaemia enhances peripheral muscle oxidative stress in chronic obstructive pulmonary disease

C Koechlin¹, F Maltais², D Saey², A Michaud², P LeBlanc², M Hayot¹, C Préfaut¹

¹ UPRES-EA 701, Laboratory of Physiologie des Interactions, Service Central de Physiologie Clinique, Hôpital Arnaud de Villeneuve, 34295 Montpellier cedex 5, France
² Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l’Université Laval, Sainte-Foy, Québec, Canada

Correspondence to:
Dr C Koechlin
Laboratoire de Physiologie des Interactions, Service Central de Physiologie Clinique, Hôpital Arnaud de Villeneuve, 34295 Montpellier cedex 5, France; christelle_koechlin{at}hotmail.com

Background: Because oxidative stress affects muscle function, the underlying mechanism to explain exercise induced peripheral muscle oxidative stress in patients with chronic obstructive pulmonary disease (COPD) is clinically relevant. This study investigated whether chronic hypoxaemia in COPD worsens peripheral muscle oxidative stress and whether an abnormal muscle inflammatory process is associated with it.

Methods: Nine chronically hypoxaemic and nine non-hypoxaemic patients performed repeated knee extensions until exhaustion. Biopsy specimens were taken from the vastus lateralis muscle before and 48 hours after exercise. Muscle oxidative stress was evaluated by lipid peroxidation (lipofuscin and thiobarbituric acid reactive substances (TBARs)) and oxidised proteins. Inflammation was evaluated by quantifying muscle neutrophil and tumour necrosis factor (TNF)- levels.

Results: When both groups were taken together, arterial oxygen pressure was positively correlated with quadriceps endurance time (n = 18, r = 0.57; p<0.05). At rest, quadriceps lipofuscin inclusions were significantly greater in hypoxaemic patients than in non-hypoxaemic patients (2.9 (0.2) v 2.0 (0.3) inclusions/fibre; p<0.05). Exercise induced a greater increase in muscle TBARs and oxidised proteins in hypoxaemic patients than in non-hypoxaemic patients (40.6 (9.1)% v 10.1 (5.8)% and 51.2 (11.9)% v 3.7 (12.2)%, respectively, both p = 0.01). Neutrophil levels were significantly higher in hypoxaemic patients than in non-hypoxaemic patients (53.1 (11.6) v 21.5 (11.2) counts per fibre x 10^–3; p<0.05). Exercise did not alter muscle neutrophil levels in either group. Muscle TNF- was not detected at baseline or after exercise.

Conclusion: Chronic hypoxaemia was associated with lower quadriceps endurance time and worsened muscle oxidative stress at rest and after exercise. Increased muscle neutrophil levels could be a source of the increased baseline oxidative damage. The involvement of a muscle inflammatory process in the exercise induced oxidative stress of patients with COPD remains to be shown.

Abbreviations: FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; GPx, glutathione peroxidase; HR, heart rate; MCTSA_CT, mid thigh muscle cross sectional area; MVC, maximal voluntary contraction; PaO₂, arterial oxygen pressure; ROS, reactive oxygen species; SOD, superoxide dismutase; SpO₂, oxygen pulse saturation; TBARs, thiobarbituric acid reactive substances; TNF-, tumour necrosis factor

Keywords: chronic obstructive pulmonary disease; exercise; hypoxaemia; lipid peroxidation; lipofuscin; oxidised protein; inflammation

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